Computational study: Synthesis, spectroscopic (UV–vis, IR, NMR), antibacterial, antifungal, antioxidant, molecular docking and ADME of new (E)-5-(1-(2-(4-(2,4-dichlorophenyl)thiazol-2-yl)hydrazineylidene)ethyl)-2,4-dimethylthiazole
Keshav B. Gangurde, Vishnu A. Adole, Dattatray S. Ghotekar
Abstract
In this paper, we describe the synthesis of a novel (E)-5-(1-(2-(4-(2,4-dichlorophenyl)thiazol-2-yl)hydrazineylidene)ethyl)-2,4-dimethylthiazole (DCPTHT) via multicomponent reaction between 1-(2,4-dimethylthiazol-5-yl)ethan-1-one, thiosemicarbazide and 2-bromo-1-(2,4-dichlorophenyl)ethan-1-one. The structure of DCPTHT was confirmed on the basis of FT-IR, 1HNMR and 13C NMR characterizations. The molecular structure of the novel thiazole derivative was examined using density functional theory (DFT) simulations at the B3LYP/6-311G (d,p) level of theory. Molecular simulations were made for total energy, HOMO and LUMO energy, and Mullikan atomic charges. In a dimethyl sulfoxide solvent, the electronic absorption spectra were acquired, and TD-DFT calculations were used to discuss the band assignments. By correlating the experimental and simulated spectra, NMR assignments and interpretations were also established. Remarkably, antibacterial and antifungal screening was used to examine the biological profile of DCPTHT. Antibacterial screening was performed against E. coli, B. subtilis, P. aeruginosa, and MRSA while the antifungal screening was performed against A. niger and C. It was found that the newly synthesized thiazole derivative demonstrated potent antifungal activity on the investigated fungus species. Molecular docking study against cytochrome P450 14α-sterol demethylase (CYP51) (PDB id: 5v5z). Furthermore, ADME predictions are also discussed. The molecular docking studies revealed mostly hydrophobic and Vander Waals interactions with different amino acid residues.